Synapse formation in developing neural circuits.
Synapse formation in developing neural circuits.
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DOI：
10.1016/s0070-2153(09)01202-2
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发表时间：
2009
影响因子：
--
通讯作者：
Colón-Ramos DA
中科院分区：
文献类型：
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作者：
Colón-Ramos DA
神经系统由数千亿个神经元组成，这些神经元相互连接成构成行为基础的功能神经网络。神经元在网络中支配和运作的能力是通过被称为突触的特殊细胞连接来调节的。突触是调节神经系统细胞间通讯的大分子结构，也是神经网络中信息流的主要守门人。突触形成的地点和时间决定了神经网络的连通性和功能。因此，我们对突触形成是如何调控的知识对于我们理解神经系统以及它在神经系统疾病中是如何出错的至关重要。突触的形成涉及到突触前和突触后伙伴在特定的神经空间坐标上配对。突触形成的特殊性需要精确执行多种发育事件，包括细胞命运指定、细胞迁移、轴突引导、树突生长、突触靶点选择和突触发生(Juttner和Rathjen in Cell)。摩尔。生命科学。62：2811,2005；Salie等人，in Neuron 45：189,2005；Waites et al.，in Annu。神经科学牧师。2005年28：251)。值得注意的是，在脊椎动物神经系统的发育过程中，这些发育过程几乎同时发生在数十亿个神经元中，导致数万亿突触的形成。这种显著的特异性是如何在发育过程中协调的，是神经生物学领域的突出问题之一，也是本章讨论的焦点。我们集中讨论这一章的早期发育事件，这些事件在活动依赖机制之前协调突触发生的过程。因此，我们限制了对重要的活动依赖的突触发生事件的讨论，这将在本书的其他章节中讨论。此外，我们的讨论偏向于我们从无脊椎动物系统中学到的教训，特别是从线虫和果蝇身上。我们这样做是为了补充本书其他章节的讨论，这些章节侧重于最近从脊椎动物文献中出现的重要发现。本章从突触生物学领域的简要历史开始。这是一个背景，介绍了突触发育的一些历史上突出的问题，这些问题在过去的一个世纪里一直没有得到我们的理解，也是本综述的重点。然后，我们讨论了突触结构的一些一般特征，因为它与其功能有关。特别是，我们将强调所有突触结构共享的进化保守特征，以及这些特征如何帮助优化这些古老的细胞连接以进行神经间通信。然后，我们讨论协调这些保守的大分子结构的精确组装的调控信号。这一讨论将在神经发育过程的背景下进行。具体地说，我们的大部分讨论将集中在看似不同的发育过程如何在分子水平上紧密联系，以及这种关系如何在电路组装的发育协调中至关重要。我们希望，对指导电路发展的多功能线索的讨论提供了一个概念框架，以理解如何在有限的信号分子集下，在突触伙伴之间协调精确的神经连接。
The nervous system consists of hundreds of billions of neurons interconnected into the functional neural networks that underlie behaviors. The capacity of a neuron to innervate and function within a network is mediated via specialized cell junctions known as synapses. Synapses are macromolecular structures that regulate intercellular communication in the nervous system, and are the main gatekeepers of information flow within neural networks. Where and when synapses form determines the connectivity and functionality of neural networks. Therefore, our knowledge of how synapse formation is regulated is critical to our understanding of the nervous system and how it goes awry in neurological disorders. Synapse formation involves pairing of the pre- and postsynaptic partners at a specific neurospatial coordinate. The specificity of synapse formation requires the precise execution of multiple developmental events, including cell fate specification, cell migration, axon guidance, dendritic growth, synaptic target selection, and synaptogenesis (Juttner and Rathjen in Cell. Mol. Life Sci. 62:2811, 2005; Salie et al., in Neuron 45:189, 2005; Waites et al., in Annu. Rev. Neurosci. 28:251, 2005). Remarkably, during the development of the vertebrate nervous system, these developmental processes occur almost simultaneously in billions of neurons, resulting in the formation of trillions of synapses. How this remarkable specificity is orchestrated during development is one of the outstanding questions in the field of neurobiology, and the focus of discussion of this chapter. We center the discussion of this chapter on the early developmental events that orchestrate the process of synaptogenesis prior to activity-dependent mechanisms. We have therefore limited the discussion of important activity-dependent synaptogenic events, which are discussed in other chapters of this book. Moreover, our discussion is biased toward lessons we have learned from invertebrate systems, in particular from C. elegans and Drosophila. We did so to complement the discussions from other chapters in this book, which focus on the important findings that have recently emerged from the vertebrate literature. The chapter begins with a brief history of the field of synaptic biology. This serves as a backdrop to introduce some of the historically outstanding questions of synaptic development that have eluded us during the past century, and which are the focus of this review. We then discuss some general features of synaptic structure as it relates to its function. In particular, we will highlight evolutionarily conserved traits shared by all synaptic structures, and how these features have helped optimize these ancient cellular junctions for interneural communication. We then discuss the regulatory signals that orchestrate the precise assembly of these conserved macromolecular structures. This discussion will be framed in the context of the neurodevelopmental process. Specifically, much of our discussion will focus on how the seemingly disparate developmental processes are intimately linked at a molecular level, and how this relationship might be crucial in the developmental orchestration of circuit assembly. We hope that the discussion of the multifunctional cues that direct circuit development provides a conceptual framework into understanding how, with a limited set of signaling molecules, precise neural wiring can be coordinated between synaptic partners.